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Abstract

Objective

To assess the predictors and prevalence of HIV infection among injection drug users
in highly endemic regions along major drug trafficking routes in three Chinese provinces.

Results

Of the 689 participants, 51.8% were HIV-infected, with persons living in Guangxi having
significantly lower prevalence (16.4%) than those from Xinjiang and Yunnan (66.8%
and 67.1%, respectively). Syphilis seropositivity was noted in 5.4%. Longer duration
of IDU, greater awareness of HIV transmission routes, and living in Xinjiang or Yunnan
were associated with HIV seropositivity on multivariable analysis. Independent risk
factors differed between sites. In Guangxi, being male and having a longer duration
of IDU were independent risk factors for HIV infection; in Xinjiang, older age and
sharing needles and/or syringes were independent factors; in Yunnan, more frequent
drug injection, greater awareness of HIV transmission routes, and higher income were
independent predictors of HIV seropositivity.

Conclusion

Prevalence rates of HIV among IDUs in China are more than two out of three in some
venues. Risk factors include longer duration of IDU and needle sharing. Also associated
with HIV were factors that may indicate some success in education in higher risk persons,
such as higher knowledge. A systemic community-level intervention with respect to
evidenced-based, population-level interventions to stem the spread of HIV from IDU
in China should include needle exchange, opiate agonist-based drug treatment, condom
distribution along with promotion, and advocacy for community-based VCT with bridges
to HIV preventive services and care.

Background

Injection drug use (IDU) represents the largest single cause of HIV transmission in
China, accounting for nearly half of the infections at the end of 2005 [1]. Ministry of Public Security data suggest that the number of registered drug users
has risen steadily at a rate of about 122% per year, from 70,000 in 1990 to 1.16 million
in 2005 [2-4]. The total number, including unregistered drug users, is thought to be much higher,
perhaps 3.5 million [5]. China has the second largest estimate (midpoint: 1.9 million) of IDUs worldwide,
following only Russia [6]. The first large outbreak of HIV in China was identified in 1989 among injection
drug users (IDUs) in Dehong Prefecture of Yunnan Province on the Myanmar (Burma) border
in southwest China [7]. The specific HIV subtypes first seen in Dehong spread along drug trafficking routes
to IDUs in nearby cities in Yunnan [8,9]. Since then, serious epidemics among IDUs have been identified in Xinjiang (1996),
Guangxi and Sichuan (1997), Guangdong (1998), Gansu (1999), and Jiangxi (2000) [10]. The HIV epidemic routes coincided with the major drug trafficking roads from the
"Golden Triangle" into China. Molecular epidemiology suggests that the major spread
of the initial drug-related epidemic in China started in Yunnan and took two major
routes: northbound to Sichuan, Guizhou, Gansu, Ningxia and Xinjiang, and eastbound
to Guangxi, Guangdong and Guizhou [8,9,11-18]. Before 1993, the HIV-infected cases in China were reported mainly from Yunnan [7].

Xinjiang and Sichuan first reported HIV infections among drug users in 1995; the HIV
epidemic was first detected among drug users in Guangxi in 1996. In subsequent years,
HIV spread rapidly among IDUs in Yunnan, Xinjiang, and Guangxi and by the end of 2002,
all 31 provinces, municipalities and autonomous regions in mainland China, as well
as Hong Kong, Macao, and Taiwan, had reported cases of HIV/AIDS among drug users from
1989 to 2004. Yunnan reported the highest number of annual HIV/AIDS cases in mainland
China [7].

Yunnan's proximity to one of the world's largest illicit drug (especially heroin)
production and distribution centers, the "Golden Triangle", contributes to drug trafficking
and the availability of heroin [12,19,20]. Only a small portion of heroin/opium is trafficked into Xinjiang from the "Golden
Crescent" [3]. Currently, Yunnan, Xinjiang and Guangxi have remained the top three of the hardest-hit
regions fueled by IDU in China [7,12,14,18,21-23]. However, no systematic community-based interventions have been undertaken in these
regions. Only a small fraction of IDUs receive counseling and testing services and
even fewer have participated in methadone maintenance treatment and needle exchange
programs that were started in 2004. Several studies have described the different HIV
transmission risk factors among IDUs based in detoxification and detention centers
in China [24,25]. However, there are few studies that used community-based recruitment of IDUs from
multiple provinces [15]. A behavioral survey among drug users in Yunnan, Xinjiang, Hubei, and Beijing found
that most of the drug users reported behaviors associated with high rates of HIV/AIDS
acquisition, such as unsafe sexual practices and using drugs intravenously (70.6%)
[23]. Of those who used drugs intravenously, 89.2% reported sharing needles. The general
knowledge about HIV/AIDS among this group was relatively poor. In order to understand
the threat of HIV epidemic expansion and guide appropriate HIV prevention among IDUs
in three highly endemic regions along drug trafficking routes in China, we conducted
this community-based survey to assess the prevalence of HIV and syphilis and predictors
for HIV infections.

Methods

Study sites

This study was conducted in three sites along major drug (heroin) trafficking routes
in Nanning City, Guangxi Zhuang Autonomous Region; Yili Prefecture, Xinjiang Uygar
Autonomous Region; and Honghe Prefecture, Yunnan Province (Fig. 1). We chose these three drug trafficking routes/provinces because HIV epidemics in
these areas shared certain characteristics. All three regions were hardest hit by
HIV, IDU has been the predominant route of transmission for HIV, and non-Han minority
ethnic groups account for a large portion of the IDUs. Most of these IDUs live in
relatively poor socioeconomic conditions.

Guangxi

, located along the major drug trafficking trade route bordering Yunnan on the west
and Vietnam on the southwest, hosts 49 million people. Nanning is Guangxi's capital
city and has a population of almost 2 million, 36% of whom belong to Zhuang ethnic
and other non-Han minority ethnic groups.

Xinjiang

covers a very large area, with 19 million people in far northwestern China, and has
the longest boundary in China. From the northeast to the southwest,

is located in southwestern China and borders Myanmar, Laos, and Vietnam. Ethnic minorities
account for 33.4% of Yunnan's population of 43 million. Honghe Prefecture is located
in the south of Yunnan Province. The population of Honghe is about 4.1 million and
40.0% belong to Hani and Yi ethnic groups, while 14.7% belong to other non-Han minorities.

Study design and study population

Community-based surveys were completed from November 2004 to January 2005. The size
of the IDU population was estimated in each community and geographic mapping was conducted
for each site in the study's targeted communities. The participants were primarily
enrolled by the trained staff using community outreach and peer referral "snowball"
techniques. The peer referrals were limited to a maximum of five participants in order
to enroll a relatively representative sample in the IDU community. Eligibility criteria
required that participants be ≥18 years old and have injected drugs at least one time
in the last three months. Blood was collected for HIV and syphilis testing. All eligible
participants were provided with risk reduction and coping counseling, both pre- and
post-test. Written informed consent was received for all participants. Survey information
was collected anonymously and remained confidential. The surveys also served as part
of ongoing comprehensive IDU-focused surveillance activity, combining behavioral and
biological information [26]. The study was approved by the Institutional Review Board (IRB) of the National Center
for AIDS/STD Control and Prevention of the China Centers for Disease Control and Prevention,
as well as the IRB of Vanderbilt University.

Measures

Participants were recruited and completed all study procedures in either Chinese and/or
the local language. All interviews were conducted by trained staff in both Chinese
and the local languages to provide information including (Table 1 and 2): (1) demographic characteristics, e.g., sex, age, marital status, residency, ethnicity,
years of education, monthly income, and study site; (2) drug use behaviors, e.g.,
duration of drug use, frequency of injecting drugs in the last week, ever shared needle
and/or syringe during injection, the number of people shared needle and/or syringe
with in the last injection, frequency of shared injection needle and/or syringe in
the last six months, always carried a needle and syringe when out, and how many times
a needle and syringe was used before trashing it; and (3) sexual behaviors, e.g.,
living with regular sex partners in the last year, ever had sex with regular sex partner
in the last year, condom use with regulars sex partners in the last sex act, frequency
of condom use with regular sex partners in the last year, regular sex partners ever
used drugs, regular sex partners knew you used drugs, shared needle and/or syringe
with regular sex partners, ever had sex with non-regular sex partners in the last
year, the number of non-regular sex partners in the last year, condom use with non-regular
sex partners in the last sex act, frequency of condom use with non-regular sex partners
in the last year, ever paid money or provided drugs for sex in the last year, the
number of sex partners paid or provided drugs for sex in the last year, condom use
during paid or provided drugs for sex in the last sex act, frequency of condom use
during paid or provided drugs for sex in the last year, ever provided sex for money
or drugs for sex in the last year, the number of sex partners who had sex for money
or drugs in the last year, condom use during sex for money or drugs in the last sex
act, and frequency of condom use during sex for money or drugs in the last year. Knowledge
about risk of HIV transmission routes was assessed by correctly answering five questions
that were related to modes of HIV transmission (blood, sex, and mother to infant).
The participants were further asked whether they had ever received voluntary HIV counseling
and testing (VCT). All of the above questions in the questionnaire were selected by
a panel of consultants of the national behavioral and biological sentinel surveillance
in China [26,27].

All collected serospecimens were stored at the Prefecture-level CDC laboratories and
transported to Provincial-level CDC for HIV testing. Two Enzyme-Linked ImmunoSorbent
Assays (ELISA, Vironostika HIV Uni-form II plus O™, BioMérieux, Marcy L'Etoile, France;
Beijing Wantai Biologic Medicine Co., China) were performed. Both samples testing
positive were considered HIV-positive; both samples testing negative were considered
HIV-negative. A repeat second ELISA was used as a tiebreaker for discordant results.
Western blot confirmation of cases was possible in one province consistently, one
province intermittently, but was not used in the third province. Syphilis serostatus
was determined by screening for the antibody to Treponema pallidum antigen (p15, p17, and p47) and by a positive rapid-plasma reagin (RPR) test (Macro-Vue
RPR™ Card Test, Becton-Dickinson, USA).

Statistical analysis

Data were entered with EpiData. After corrections, data were then converted and analyzed
using the Statistical Package for the Social Sciences (SPSS 15 for Windows™; SPSS
Inc., Chicago, Il, USA). The data were analyzed using unadjusted odds ratios with
95% confidence intervals for the odds ratio point estimates. Tests for significance
of categorical data used a Chi-square test or Fisher's exact test. A multivariable
logistic regression model was constructed with all variables in the univariate model
whose p value was less than 0.2. Thus, we report independent risk factors for HIV
infection, controlling for confounding and interaction from other putative risk factors.

Results

Socio-demographic characteristics

We included 689 eligible participants (95.4%) for the analyses; 33 persons were excluded
because of refusing to participate or not meeting eligibility criteria. Of the participants,
82.0% were males; 53.8% were of the majority Han ethnicity; 72.4% had <6 years of
education; and 59.0% were single, 29.1% married, and 11.9% separated (Table 1). Their average age was 30.8 years old (S.D. ± 6.0) and 40.0% were under 30 years
old; 97.5% were local residents; and 54.2% had ≤ 300 Yuan monthly incomes (Table 1).

HIV knowledge and VCT

Of the participants, 80.9% were aware of all three transmission routes (blood, sex,
and mother-to-child); only 5.1% of the participants had ever received VCT (Table 2).

Drug use and sexual behaviors

Of the participants, 79.1% had used illicit drugs >5 years; 79.1% injected drugs for
≥ 5 years; and 51.0% reported a history of sharing needles and/or syringes. To judge
current users, we determined that 27.2% had injected drugs more than twice in the
prior week. Of the 11.7% participants who reported using a shared needle and/or syringe
in the last injection, three-quarters of them shared with more than one person. Of
the participants, 70.5% reported never carrying a needle and syringe when they were
out. 54.3% of the participants reported used a needle and syringe more than once before
trashing it. One-fifth of participants reportedly had sex with non-regular partners
in the last year. One-third of subjects reported always using condoms when having
sex with their regular partner in the last year, while 40.0% reported always using
condoms when having sex with non-regular sex partners in the last year. Over the last
year, 7.5% had paid money or provided drugs for sex and only 12.5% of them reported
using condoms consistently. 29.1% provided sex for money or drugs and none of them
reported using condoms consistently (Table 2).

Prevalence of syphilis seropositivity and predictors for HIV seropositivity

Of the 689 participants, 5.4% were RPR reactive for syphilis. 51.8% were HIV-seropositive,
with persons living in Guangxi having significantly lower prevalence (16.4%) than
those from Xinjiang and Yunnan (66.8% and 67.1%, respectively). In univariate analyses,
risk factors associated with HIV sero-positive status included male sex, "separated"
marital status, local residency, minority (i.e., non-Han) ethnicity, study site (Yili,
Xinjiang and Honghe, Yunnan), awareness of HIV transmission routes, having received
VCT, longer duration of drug use, and longer duration of IDU (Table 1 and 2). Sexually-related factors, age, years of education, and syphilis seropositivity
were not associated significantly with HIV seropositive status.

Table 3. Factors associated with HIV infection among injection drug users in three highly endemic
regions of China, as predicted by a multivariable logistic regression model

Discussion

We assessed the prevalence and predictors of HIV sero-positive among 689 IDUs with
serious illicit drug problems in China using community-based cross sectional surveys
with consistent sampling procedures in all three provinces (or autonomous regions).
HIV prevalence was very high (51.8%), but was lower in persons living in Guangxi (16.4%)
compared to Xinjiang and Yunnan (67.8%). The HIV prevalence rates were remarkably
similar to those from the same sites among IDUs from detoxification or detention centers
[22], and were significantly higher than estimates from community-based surveys in other
regions in China [27].

Lower rates are reported in other provinces. For example, in January 2005, HIV prevalence
rates of 0% to 5.9% were reported in six community-based surveys of 1,260 IDUs in
Guangxi and Yunnan's adjacent provinces of Sichuan (3.7%), Guangdong (5.9%), and Guizhou
(0%), with even lower prevalence noted in sites in Fujian (0.4%), Henan (0%), and
Hubei (0%), provinces located farther from Guangxi and Yunnan [27]. Higher HIV prevalence rates among IDUs in 2004–2006 surveys are seen in those regions
of Guangxi, Xinjiang, and Yunnan where rapid spread of the virus among drug users
occurred earliest; HIV was first reported in Yunnan in 1989 [7,22]. Overall prevalence was noted to be 71.9% among IDUs from detoxification centers
in Honghe and Wenshan Prefectures of Yunnan Province in 2000, having declined subsequently.
One may speculate that rates have dropped due to deaths and/or prevention successes
[28]. Five out of 15 prefectures in Yunnan have reported high HIV prevalence rates among
IDUs, ranging from 48.9% to 75.0% [7,22,29]. Biological sentinel surveillance data show that HIV prevalence rates have reached
75.0% in certain sites of Xinjiang and 51.0% in certain sites of Guangxi in 2005 [22]. The majority of the participants in sentinel surveillance were recruited from detoxification
or detention centers and they are likely to be higher risk injectors than IDUs in
community settings. These differences could also reflect the availability of proactive
testing in the detoxification or detention centers rather than a proven difference
between the sub-group and a wider population of IDUs.

High HIV prevalence among IDUs, prevalent needle sharing and high frequency of injecting
practices suggest an urgent need to improve drug addiction treatment and risk reduction
measures in China. We found that 51.0% of the participants had shared needles and/or
syringes and 27.2% had injected drugs more than twice in the last week. An HIV epidemic
becomes self-perpetuating (endemic) and even a modest level of risk behavior can lead
to a substantial rate of infection in the face of efficient needle/blood transmission
[30,31]. Because they live along major drug trafficking routes, many of the HIV-infected
IDUs in our survey will continue to serve as a major source for continued transmission
and further spread unless drug abuse treatment, antiretroviral therapy, and risk reduction
are implemented, as indicated[32].

While longer duration of IDU, shared injection needle and/or syringe, and higher frequency
of injection were the independent risk factors for HIV infection [14,15,33,34], greater awareness of HIV was associated (unexpectedly) with higher HIV prevalence.
This may suggest some successes in educating IDUs. Higher income was also a risk factor.
We speculate that drug users with higher incomes may use drugs more often; they may
also have a greater awareness of HIV issues. There was some diversity in associated
risk factors among the IDU subgroups in the three regions where HIV prevalence was
especially high. Although a high portion of participants know HIV transmission routes
in all three sites, the needle sharing rates and unprotected sexual behaviors were
still high among IDUs. Most astonishingly, a very small portion (overall 5.1%) of
participants reported ever receiving VCT, a gateway for the prevention programs. This
indicated that a large proportion of IDUs who have been infected with HIV don't know
their status and could continue to spread the virus [26,35]. China has scaled up HIV control efforts since 2004 [35]; however, low HIV testing rates (≈20% nationwide) remain an impediment to prevention
and care. Lack of affordable accessibility to sterile needles and syringes was the
major reason for high risk sharing of "works" in this study. Other data suggested
social norms that foster stigma, discrimination associated with drug use and HIV/AIDS,
fear of arrest due to illegal practice, knowing a positive result, a lack of coping
skills, and knowledge of HIV risks are the other reasons for the low rate of HIV testing
among IDUs [4,26]. This suggested that risk reduction education alone cannot help drug users and their
sex partners make lasting behavioral changes. The community-based needle exchange
programs and elimination of any barriers to accessing clean needles and syringes could
reduce the prevalence of needle sharing among IDUs[36,37]. In addition to providing accurate and up-to-date information on risky behaviors,
effective community-based prevention programs not only make clean needles and condoms
available and accessible, but also focus on enhancing individuals' motivation to change
their behavioral patterns, teaching concrete strategies, and behavioral skills to
reduce risk, providing tools for risk reduction, and reinforcing positive behavior
change.

We found that there were significant differences between sex, age, marital status,
residency, ethnicity, education level, and monthly income among the participants in
the three study sites. A larger portion of participants who were single and belong
to the Han ethnic group, with >6 years of education and higher income, were recruited
in Honghe, Yunnan than in the other two sites. Yili, Xijiang's participants were more
likely to be younger, belong to non-Han ethnic groups (86.9% Wei ethnic group in Yili,
Xijiang; 11.2% Hani and Yi ethnic groups in Honghe, Yunnan and 32.2% Zhuang ethnic
group in Nanning, Guangxi), and receive lower levels of education. Nanning, Guangxi's
participants were more likely to have less monthly income (74.2% with ≤ 300 Yuan RMB
monthly income). We found that higher income in Honghe, being male in Nanning, and
old age in Yili were independently associated with HIV infection. There could be other
factors beyond this study, besides gender, age and the sharing of needles, such as
the actual availability of syringe distribution and exchange programs, condom distribution
and promotion, and other social determinants of health that account for the differences
for the HIV prevalence rates in the three study sites. China's central government
has scaled up HIV/AIDS control efforts since 2004 [35], including setting up national policy framework for responding to HIV/AIDS, increasing
funding inputs, and expanding collaborations with international organizations. However,
responses to drug use and the HIV/AIDS epidemic vary significantly at provincial and
lower administrative levels. A literature review indicated that Yunnan and Guangxi
provinces have done far more than other provinces in supporting, implementing, and
advocating for harm reduction interventions for IDUs [4]. Some local governments are not fully motivated to confront drug abuse and HIV/AIDS
problems [4].

Among IDUs in other studies from China, risky sexual behaviors have been reported
as a risk factor for HIV infection [14,15,34], although we did not find this association in our three populations. Most of our
participants that lived in remote rural areas of Honghe, Yunnan and Yili, Xinjiang
were less likely to receive health education and services. Furthermore, due to relatively
poor economic status and lower levels of education, they may be more likely to be
involved in drug smuggling and abuse, and unprotected sexual behavior. Risk reduction
programs should give high priority to these poorer, more isolated IDUs who are also
more likely to be of minority ethnic origin. Because of the high prevalence of HIV
and often risky sexual behavior among IDUs, there is a great potential for IDUs serving
as a bridge population to transmit HIV to the general population. The overlapping
of risk behaviors among at-risk persons facilitates the rapid HIV spread from IDUs
to other risk groups, e.g., from female sex workers and their clients to their clients'
regular partners. We found that low condom use rates and the high proportion of female
drug users who had reported engaging in commercial sex underscore the importance of
behavioral surveillance in IDUs to provide early warnings and more effective interventions.
This highlighted the need for condom distribution and promotion. As noted in this
study, most of the target IDUs interviewed already knew the causes of HIV; the problem
is not knowledge translation, it is more basic social determinants of health. They
don't have access to free condoms. Free condoms should be provided widely to sex trade
workers and IDUs.

The prevalence of syphilis by RPR in our high risk IDUs was 5.4% (33/647), similar
to estimates in 10 sentinel surveillance sites using RPR screening in 1,414 IDUs in
the same three provinces (average: 6.6%, range from 1.2 to 14.1%) [22]. Syphilis seropositivity did not predict HIV, suggesting that most infections were
due to injection-related behaviors. Other studies have reported an association between
HIV infection and other STDs among IDUs [38-41]. Syphilis should be considered one indicator of high sexual risk behavior among IDUs
[42]. Previous studies of syphilis among IDUs have suggested that while a high prevalence
of syphilis and low HIV prevalence may be found in clinical or community settings,
the reverse pattern of high HIV prevalence and low prevalence of syphilis may be more
common in detoxification centers where IDUs, who are heavier drug users, are overrepresented
[22,43]. The patterns of STD co-morbidity among IDUs vary significantly by venue and high
risk group [22,44].

Strengths of this study include its substantial sample size, the geographic diversity
of our venues, and community-based outreach and peer referral using "snowball" and
mapping strategies. There are also limitations. First, IDUs recruited into the study
may have been higher risk such that their HIV prevalence may not exactly reflect the
true background rate among IDUs in the study community. Second, recall bias and social
desirability bias are possible, since the drug use and sexual behavioral information
was collected based on self-reporting. Most information about drug use and sexual
behaviors in the last year were used in the data collection, instead of collecting
the behaviors in more recent period, in the last three or six months. Third, our cross-sectional
study cannot ascertain a causal association between predictors and HIV infections.
Fourth, we do not include a complete list of factors in this study. Other factors
beyond this study may also account for the differences.

China has initiated harm reduction projects, including needle exchange programs, methadone
treatment, condom promotion, and VCT programs among drug users [4,25,36,37,45,46]. China Center for Disease Control and Prevention provincial authorities have been
organizing the needle exchange and methadone treatments since early 2004 [20,46,47]. China plans to scale up harm reduction projects, including needle exchange programs
and methadone treatments, since only a small portion of IDUs have been covered by
these programs so far. Our data suggest the urgent need for expanded community-level
needle exchange programs, opiate agonist-based drug treatment, and advocacy for community-based
VCT with bridges to HIV preventive services and care. Condom distribution along with
condom promotion should also be highlighted. In vulnerable target populations where
condom use is directly related to availability, condom distribution and promotion
is crucial to helping curb the spread of HIV and other STDs. These prevention and
treatment efforts are likely to require an infrastructure that not only provides operational
and financial support, but also creates an environment in which IDUs feel comfortable
and safe in seeking help without any barriers. Implementation research programs can
critically assess these programs and provide insight as to where they might be improved.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

YJ participated in the development of the manuscript, coordinated the analysis, and
drafted the manuscript. FL, ZG, and XS were responsible for securing funding, supervising
data collection, and preparation of the manuscript. YX provided data analysis, and
drafted and reviewed the manuscript. CL and PW served as the statisticians for the
manuscript. LW, LL, MN, and SQ oversaw all recruitment efforts in the field, supervised
HIV and syphilis tests, and were an active part of the preparation of the manuscript.
SHV provided input with guidance on the data analysis and interpretation, and co-wrote
the manuscript. All authors read and approved the final manuscript.

Acknowledgements

This work was jointly supported by the National Center for AIDS/STD Control and Prevention,
the Chinese Centers for Disease Control and Prevention, the Guangxi Zhuang Autonomous
Regional Centers for Disease Control and Prevention, the Xinjiang Uygar Autonomous
Regional Centers for Disease Control and Prevention, the Yunnan Provincial Centers
for Disease Control and Prevention, the U.S. National Institutes of Health (grants
numbers R03AI067349 and D43TW001035), and Vanderbilt University School of Medicine
Institute for Global Health.

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